@misc{10481/76019, year = {2022}, month = {5}, url = {http://hdl.handle.net/10481/76019}, abstract = {Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM-10 mu M). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPAR gamma, C/EBP alpha, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 mu M. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPAR gamma, C/EBP alpha, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 mu M and lesser expression at 1 mu M. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1-10 mu M) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing.}, organization = {European Commission 733032}, organization = {Biomedical Research Networking CenterCIBER de Epidemiologia y Salud Publica (CIBERESP) of the Institute of Health Carlos III European Commission FIS-PI16/01820 FIS-PI16/01812 FIS-PI16/01858}, organization = {Spanish Government FPU 17/01848}, publisher = {MDPI}, keywords = {Mixtures}, keywords = {Bisphenols}, keywords = {Bisphenol A (BPA)}, keywords = {Bisphenol S (BPS)}, keywords = {Bisphenol F (BPF)}, keywords = {Endocrine disruptors}, keywords = {Dose addition}, title = {The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells}, doi = {10.3390/toxics10060287}, author = {Reina Pérez, Iris and Olivas Martínez, Alicia and Mustieles Miralles, Vicente and Salamanca Fernández, Elena and Molina Molina, José Manuel and Olea Serrano, Nicolás and Fernández Cabrera, Mariana Fátima}, }